In our screening program on immunomodulatory components from fungi, crude extracts of several fungi among ca. 150 species of fungi showed significantly suppressive activity against blastogenesis of mouse splenic lymphocytes. Chromatographic fractionations of these active extracts guided by immunosuppressive activity afforded several immunosuppressive constituents, namely, nine new 2-pyrones, multiforisins A(1)-I(9), from Gelasinospora multiforis, a new macrocyclic sesterterpene kobiin (10), and three new 2-furanones, kobifuranones A(11)- C(13), from Gelasinospora kobi, a 2-pyrone, macrophin(14) (a metaboilte of Macrophoma commelinae), two macrocyclic lactones, colletodiol(15) (a metabolite of Colletotricum capsici and Chaetomium funicola) and its new stereoisomer 10-epi-colletodiol(16) from Diplogelasino- spora grovesii, 7-9 and a hexaketide, sordarial(17) (a metabolite of Sordaria macrospora), from Gelasinospora heterospora, and 1, 7-9, and 17 from Gelasinospora longispora. To our kno
… Morewledge, this is the first time that the three known components 14, 15, and 17 have been isolated as immunosuppressive constituents from natural sources, and the absolute. configuration of the side chain in 17, which had been not yet decided, has been completely determined this time. Structure-activity relationship of immunosuppressive 2-pyrones including twelve compounds, namely, 1-9, two their derivatives and 14, has been elucidated. Comparison of the mode of action of one of the multiforisins, 7, with that of FK506 indicated that the immunosuppressive activity of 7 was not due to inhibition of interleukin 2 production. Other some immunosuppressive components have been also isolated from Gelasinospora santi-florli, Microascus tardifaciens, and other several Ascomycetes, and their structures were also elucidated.これら活性成分中、既知化合物であった14、15、17について免疫抑制活性が見出されたのは今回が初めてであり、17については未定であった側鎖の絶対配置を今回決定した。今回得られた多数の免疫抑制活性成分中、2-ピロン化合物は1、14など比較的高い活性を有するものを含み、構造も比較的単純であるため、医薬品開発への先導化合物としての利用の可能性を考えて、1-9、それらの誘導体2種及び14の合計12種の2-ピロン化合物について構造活性相関を検討し、multiforisin類などの2-ピロン化合物の活性発現に必要な構造要因を解明した。又、免疫抑制剤FK506の作用発現様式との比較から、7の免疫抑制作用はインターロイキン2(IL-2)産生阻害によるものではないと推定した。その他、Gelasinospora santi-florilやMicroascus tardifaelensから各活性成分を単離して構造を解明し、更に、他の数種の子嚢菌からも活性成分を単離した。 Less